New anti-hepatocellular injury drugs with better curative effects and fewer side effects are urgently needed at present. In this study, a series of novel N-acetylcysteine (NAC) derivatives were designed, synthesized and biologically evaluated for their anti-hepatocellular injury activities against two different cell models. In the biological evaluation against hydrogen peroxide (H₂O₂)-induced LO2 hepatocytes, half of the target compounds exhibited moderate to potent activities in improving the model cell viability, and two compounds (6a and 6b) displayed more potent activities in decreasing malondialdehyde (MDA) levels than the positive control NAC. In further 4-acetamidophenol (APAP)-induced LO2 cell experiment, compounds 6a and 6b could not only improve the cell viability but also significantly reduce the secretion of MDA. Additionally, compound 6a displayed excellent Caco-2 permeability and oral bioavailability in rats. All these experimental results suggested that compounds 6a and 6b could serve as potential lead molecules for further development of anti-hepatocellular injury drugs.

中文翻译：

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鉴定用于治疗肝细胞损伤的新型N-乙酰半胱氨酸衍生物

目前迫切需要新的抗肝细胞损伤药物，其具有更好的疗效和更少的副作用。在这项研究中，设计，合成和生物学评估了一系列新颖的N-乙酰半胱氨酸（NAC）衍生物对两种不同细胞模型的抗肝细胞损伤活性。在针对过氧化氢（H ₂ O ₂）诱导的LO2肝细胞的生物学评估中，一半的目标化合物在改善模型细胞生存力方面表现出中度至强效的活性，另外两种化合物（6a和6b）在降低丙二醛（MDA）水平方面显示出比阳性对照NAC更有效的活性。在进一步的4-乙酰氨基苯酚（APAP）诱导的LO2细胞实验中，化合物6a和6b不仅可以提高细胞活力，而且可以显着降低MDA的分泌。此外，化合物6a在大鼠中显示出出色的Caco-2渗透性和口服生物利用度。所有这些实验结果表明，化合物6a和6b可作为潜在的先导分子用于抗肝细胞损伤药物的进一步开发。